Title : Calcium - Dependent Phosphorylation Regulates Neuronal Stability 1 and Plasticity in a Highly

39 Specific types of neurons show stable, predictable excitability properties while 40 other neurons show transient adaptive plasticity of their excitability. However, little 41 attention has been paid to how the cellular pathways underlying adaptive plasticity 42 interact with those that maintain neuronal stability. We addressed this question in the 43 pacemaker neurons from a weakly electric fish because these neurons show a highly 44 stable spontaneous firing rate as well as an NMDA receptor-dependent form of plasticity. 45 We found that basal firing rates were regulated by a serial interaction of conventional 46 and atypical PKC isoforms and that this interaction establishes individual differences 47 within the species. We observed that NMDA receptor-dependent plasticity is achieved 48 by further activation of these kinases. Importantly, the PKC pathway is maintained in an 49 unsaturated baseline state to allow further Ca-dependent activation during plasticity. 50 On the other hand, the Ca/calmodulin-dependent phosphatase calcineurin does not 51 regulate baseline firing but is recruited to control the duration of the NMDA receptor52 dependent plasticity and return the pacemaker firing rate back to baseline. This work 53 illustrates how neuronal plasticity can be realized by biasing ongoing mechanisms of 54 stability (e.g. PKC) and terminated by recruiting alternative mechanisms (e.g. 55 calcineurin) that constrain excitability. We propose this as a general model for regulating 56 activity dependent change in neuronal excitability. 57 58